ES2731823T3 - Derivados de amida para el agonista del GPR119 - Google Patents

Derivados de amida para el agonista del GPR119 Download PDF

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Publication number: ES2731823T3
Authority: ES; Spain
Prior art keywords: piperidine; methoxy; carboxamide; fluoro; hydroxypyrrolidine
Prior art date: 2013-11-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

ES14866648T

Other languages

English (en)

Spanish (es)

Inventor

Yuntae Kim

Changsik Lee

Daekyu Choi

Moosung Ko

Younghue Han

Soyoung Kim

Jaeki Min

Dohoon Kim

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Chong Kun Dang Corp

Original Assignee

Chong Kun Dang Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2013-11-26

Filing date

2014-11-25

Publication date

2019-11-19

2014-11-25 Application filed by Chong Kun Dang Corp filed Critical Chong Kun Dang Corp

2019-11-19 Application granted granted Critical

2019-11-19 Publication of ES2731823T3 publication Critical patent/ES2731823T3/es

Status Active legal-status Critical Current

2034-11-25 Anticipated expiration legal-status Critical

Links

150000001408 amides Chemical class 0.000 title claims abstract description 25
AJJISMLYIMQAKP-OAHLLOKOSA-N 5-[4-[(2r)-4-(3-fluoro-4-methylsulfonylphenoxy)butan-2-yl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(N2CCC(CC2)[C@H](C)CCOC=2C=C(F)C(=CC=2)S(C)(=O)=O)=N1 AJJISMLYIMQAKP-OAHLLOKOSA-N 0.000 title claims description 5
229940100607 GPR119 agonist Drugs 0.000 title claims description 5
-1 (1 - ((1- (trifluoromethyl) cyclobutyl) methyl) piperidine-4-yl) methoxy Chemical group 0.000 claims abstract description 259
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 105
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 80
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 64
150000003839 salts Chemical class 0.000 claims abstract description 32
229910052736 halogen Inorganic materials 0.000 claims abstract description 28
150000002367 halogens Chemical class 0.000 claims abstract description 28
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 20
VLJNHYLEOZPXFW-UHFFFAOYSA-N pyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1 VLJNHYLEOZPXFW-UHFFFAOYSA-N 0.000 claims abstract description 16
229910052799 carbon Inorganic materials 0.000 claims abstract description 11
NKLYVCPMMWKOTK-RLWLMLJZSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F NKLYVCPMMWKOTK-RLWLMLJZSA-N 0.000 claims abstract description 7
150000001721 carbon Chemical group 0.000 claims abstract description 7
OZAZXPYTQNNGFK-QPPBQGQZSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N OZAZXPYTQNNGFK-QPPBQGQZSA-N 0.000 claims abstract description 6
GEDGOYSBBTZKPG-CZWSTGFNSA-N (2S,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC1)(C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N)F)(CC)F GEDGOYSBBTZKPG-CZWSTGFNSA-N 0.000 claims abstract description 6
CQNIDDUGELWDSD-KCWPFWIISA-N (2S,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N)(CC)F CQNIDDUGELWDSD-KCWPFWIISA-N 0.000 claims abstract description 6
JQHFYBKPNAUARN-OFNKIYASSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C JQHFYBKPNAUARN-OFNKIYASSA-N 0.000 claims abstract description 6
MZWYKVKIBULCQG-GCJKJVERSA-N (2S,4R)-1-[2-fluoro-6-[4-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=CC=C1)C1=CC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N MZWYKVKIBULCQG-GCJKJVERSA-N 0.000 claims abstract description 6
LCSDJVHNINVYTD-YKSBVNFPSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=NC(=NC1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F LCSDJVHNINVYTD-YKSBVNFPSA-N 0.000 claims abstract description 6
125000000217 alkyl group Chemical group 0.000 claims abstract description 6
GEDGOYSBBTZKPG-JRSXUWQBSA-N (2R,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC1)(C(=O)N1[C@H](C[C@H](C1)O)C(=O)N)F)(CC)F GEDGOYSBBTZKPG-JRSXUWQBSA-N 0.000 claims abstract description 5
OQZWGSBSYFDEEN-NLFFAJNJSA-N (2S,4R)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N OQZWGSBSYFDEEN-NLFFAJNJSA-N 0.000 claims abstract description 5
OFPRAAREYZLWJB-RDGATRHJSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=CC=CC1)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N OFPRAAREYZLWJB-RDGATRHJSA-N 0.000 claims abstract description 5
LIMLIOLTRBZZOA-VGSWGCGISA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F LIMLIOLTRBZZOA-VGSWGCGISA-N 0.000 claims abstract description 5
CYBVBXICIDHGSV-XXBNENTESA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F CYBVBXICIDHGSV-XXBNENTESA-N 0.000 claims abstract description 5
IOOPNHMWEMBOCV-RLWLMLJZSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-3-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=C(C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F IOOPNHMWEMBOCV-RLWLMLJZSA-N 0.000 claims abstract description 5
BQHSNFJVTVGPCI-OFNKIYASSA-N (2S,4R)-1-[4-[6-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F BQHSNFJVTVGPCI-OFNKIYASSA-N 0.000 claims abstract description 5
DHTYMFQWSPOWTF-RDGATRHJSA-N (2S,4R)-1-[4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F DHTYMFQWSPOWTF-RDGATRHJSA-N 0.000 claims abstract description 5
DMZCGDNJMHFSCR-RPBOFIJWSA-N (2S,4R)-1-[4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)(CC)F DMZCGDNJMHFSCR-RPBOFIJWSA-N 0.000 claims abstract description 5
YRZOIXCPYZEUKK-BVAGGSTKSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(CC)(F)CC)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N YRZOIXCPYZEUKK-BVAGGSTKSA-N 0.000 claims abstract description 4
FJFKJVUJCQNRPU-DVECYGJZSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C FJFKJVUJCQNRPU-DVECYGJZSA-N 0.000 claims abstract description 4
JYNXPHHATOZOJR-NLFFAJNJSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F JYNXPHHATOZOJR-NLFFAJNJSA-N 0.000 claims abstract description 4
BZXKMDYEBFGWKH-QPPBQGQZSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F BZXKMDYEBFGWKH-QPPBQGQZSA-N 0.000 claims abstract description 4
OFRWTSDWAANLDL-VGSWGCGISA-N (2S,4R)-1-[3-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F OFRWTSDWAANLDL-VGSWGCGISA-N 0.000 claims abstract description 4
CLBUANMFCJHLFX-RDGATRHJSA-N (2S,4R)-1-[4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-3-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=C(C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F CLBUANMFCJHLFX-RDGATRHJSA-N 0.000 claims abstract description 4
KIEVEKHGLJYLAL-QPPBQGQZSA-N (2S,4R)-1-[3-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC1C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F KIEVEKHGLJYLAL-QPPBQGQZSA-N 0.000 claims abstract description 3
BFZPYNZHHWFLFR-UHFFFAOYSA-N 1-hydroxypyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1O BFZPYNZHHWFLFR-UHFFFAOYSA-N 0.000 claims abstract 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
206010012601 diabetes mellitus Diseases 0.000 claims description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
AFPKPVGMMLNSED-DVECYGJZSA-N (2S,4R)-1-[3-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C AFPKPVGMMLNSED-DVECYGJZSA-N 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
AUBVCQAVMLBGBA-KOSHJBKYSA-N (2S,4R)-1-[2-fluoro-6-[2-fluoro-4-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C=CC(=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N AUBVCQAVMLBGBA-KOSHJBKYSA-N 0.000 claims description 4
LXRUDSRTBHXMKW-MNNSJKJDSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC(=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=C1)F)(CC)F LXRUDSRTBHXMKW-MNNSJKJDSA-N 0.000 claims description 4
MSLGZWGSOARYCO-NDEPHWFRSA-N (2s)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CC=C(C=2C=C(F)C(C(=O)N3[C@](CCC3)(C)C(N)=O)=CC=2)N=C1 MSLGZWGSOARYCO-NDEPHWFRSA-N 0.000 claims description 4
OEZCFAIKPVTJPP-PMERELPUSA-N (2S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@](CCC1)(C(=O)N)C OEZCFAIKPVTJPP-PMERELPUSA-N 0.000 claims description 3
OWOJQYAGQCYCJQ-PMERELPUSA-N (2S)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@](CCC1)(C(=O)N)C OWOJQYAGQCYCJQ-PMERELPUSA-N 0.000 claims description 3
JVOWWOYNBNJRJH-MHZLTWQESA-N (2S)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=N1)OCC1CCN(CC1)CC(C)(C)F JVOWWOYNBNJRJH-MHZLTWQESA-N 0.000 claims description 3
AJMGFQCAPWOQFY-PIKZIKFNSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F AJMGFQCAPWOQFY-PIKZIKFNSA-N 0.000 claims description 3
IWYOTXJJAVEZAF-BVAGGSTKSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)(CC)F IWYOTXJJAVEZAF-BVAGGSTKSA-N 0.000 claims description 3
208000030159 metabolic disease Diseases 0.000 claims description 3
DFEOSUGIUZLMBC-YKGWIAGDSA-N (2R,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@](C[C@H](C1)O)(C(=O)N)C DFEOSUGIUZLMBC-YKGWIAGDSA-N 0.000 claims description 2
XCEPJRUHUZQHCE-VWLOTQADSA-N (2S)-1-[2-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F XCEPJRUHUZQHCE-VWLOTQADSA-N 0.000 claims description 2
MVQBFLZQZYHJST-VWLOTQADSA-N (2S)-1-[3-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F MVQBFLZQZYHJST-VWLOTQADSA-N 0.000 claims description 2
HLRVESUUZAJCMZ-LJAQVGFWSA-N (2S)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC(=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=C1)F)(CC)F HLRVESUUZAJCMZ-LJAQVGFWSA-N 0.000 claims description 2
DFEOSUGIUZLMBC-RCRUUEGKSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@](C[C@H](C1)O)(C(=O)N)C DFEOSUGIUZLMBC-RCRUUEGKSA-N 0.000 claims description 2
VYQKLTJBYVSQAQ-NGOKVRLYSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C)(C)F VYQKLTJBYVSQAQ-NGOKVRLYSA-N 0.000 claims description 2
XCOOKCBBWXGEHN-NGOKVRLYSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C XCOOKCBBWXGEHN-NGOKVRLYSA-N 0.000 claims description 2
BRIIVKRLAJNCJN-PIKZIKFNSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C BRIIVKRLAJNCJN-PIKZIKFNSA-N 0.000 claims description 2
VTNXFSRMYVYBPH-MNNSJKJDSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-3-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=C(C=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=C1)F)(CC)F VTNXFSRMYVYBPH-MNNSJKJDSA-N 0.000 claims description 2
LZMAQARFMZZTRU-GIGWZHCTSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=C1)(CC)F LZMAQARFMZZTRU-GIGWZHCTSA-N 0.000 claims description 2
HYKXWDZRCRYNCN-IRPSRAIASA-N (2S,4R)-1-[4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=C1)(CC)F HYKXWDZRCRYNCN-IRPSRAIASA-N 0.000 claims description 2
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QXTDHLPYNDPQBT-NDEPHWFRSA-N (2S)-1-[2-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C QXTDHLPYNDPQBT-NDEPHWFRSA-N 0.000 claims 1
BPSXABNONWEDDH-NDEPHWFRSA-N (2S)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F BPSXABNONWEDDH-NDEPHWFRSA-N 0.000 claims 1
UBEBWEZASMMAOZ-NDEPHWFRSA-N (2S)-1-[2-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F UBEBWEZASMMAOZ-NDEPHWFRSA-N 0.000 claims 1
DLVOZIGFZPAJLD-NDEPHWFRSA-N (2S)-1-[3-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC1C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F DLVOZIGFZPAJLD-NDEPHWFRSA-N 0.000 claims 1
VKCGFMPWZWGGLO-DFXYEROKSA-N (2S,4R)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@](C[C@H](C1)O)(C(=O)N)C VKCGFMPWZWGGLO-DFXYEROKSA-N 0.000 claims 1
SCMVCTBFQOMYES-DFHRPNOPSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F SCMVCTBFQOMYES-DFHRPNOPSA-N 0.000 claims 1
IIXOJZCNRQAQIQ-DFHRPNOPSA-N (2S,4R)-1-[3-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC1C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F IIXOJZCNRQAQIQ-DFHRPNOPSA-N 0.000 claims 1
CWYJVAWNERNGBC-XCZPVHLTSA-N (2S,3S)-1-[2-[2-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(CC)(F)CC)C=1C(=C(C=CC1)F)C(=O)N1[C@@H]([C@H](CC1)O)C(=O)N CWYJVAWNERNGBC-XCZPVHLTSA-N 0.000 abstract description 3
JEBNKEQXWUUHOV-IGKIAQTJSA-N (2S,3S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-3-fluorophenyl]-6-fluorobenzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=C(C=C(C=C1)C=1C(=C(C=CC1)F)C(=O)N1[C@@H]([C@H](CC1)O)C(=O)N)F)(CC)F JEBNKEQXWUUHOV-IGKIAQTJSA-N 0.000 abstract description 3
VDDFYQSPTNHOLY-CPJSRVTESA-N (2S,4S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)N VDDFYQSPTNHOLY-CPJSRVTESA-N 0.000 abstract description 3
IUYIFMVJWPVRGH-PMWNSHPQSA-N (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-fluoropyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC1)(C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)N)F)(CC)F IUYIFMVJWPVRGH-PMWNSHPQSA-N 0.000 abstract description 3
GYUJAJCZWAMFQX-CXBRBUDWSA-N (2S,3S)-1-[1-fluoro-2-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]cyclohexa-2,4-diene-1-carbonyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound FC1(C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)N1[C@@H]([C@H](CC1)O)C(=O)N GYUJAJCZWAMFQX-CXBRBUDWSA-N 0.000 abstract description 2
DRUOOQCZVQUGDG-SVBPBHIXSA-N (2S,3S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-2-fluorophenyl]benzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC(=C(C=C1)C=1C(=CC=CC1)C(=O)N1[C@@H]([C@H](CC1)O)C(=O)N)F)(CC)F DRUOOQCZVQUGDG-SVBPBHIXSA-N 0.000 abstract description 2
QYKAWRPGYZBFEG-NLFFAJNJSA-N (2S,4R)-1-[3-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F QYKAWRPGYZBFEG-NLFFAJNJSA-N 0.000 abstract description 2
KLLRIYYOHXYLOY-NVQXNPDNSA-N (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)N)(CC)F KLLRIYYOHXYLOY-NVQXNPDNSA-N 0.000 abstract description 2
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JDBDYJQOYOWMRS-UPVQGACJSA-N (2S,3S)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H]([C@H](CC2)O)C(=O)N)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F JDBDYJQOYOWMRS-UPVQGACJSA-N 0.000 abstract 1
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KBRGGSBEJZDZPC-UHFFFAOYSA-N 5-bromo-2-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridine Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(Br)C=N1 KBRGGSBEJZDZPC-UHFFFAOYSA-N 0.000 description 2
UCJOGCXLFKVRHD-UHFFFAOYSA-N 5-bromo-2-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridine Chemical compound C1CN(CC(C)(C)C(F)(F)F)CCC1COC1=CC=C(Br)C=N1 UCJOGCXLFKVRHD-UHFFFAOYSA-N 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
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DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
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MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
229940100389 Sulfonylurea Drugs 0.000 description 2
QCKFXHDNYRJAHL-UHFFFAOYSA-N [4-[(4-bromophenoxy)methyl]piperidin-1-yl]-[1-(trifluoromethyl)cyclobutyl]methanone Chemical compound C1CC(COC=2C=CC(Br)=CC=2)CCN1C(=O)C1(C(F)(F)F)CCC1 QCKFXHDNYRJAHL-UHFFFAOYSA-N 0.000 description 2
230000002411 adverse Effects 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
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JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical class N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
SABBFVWMIYCPKH-UHFFFAOYSA-N ethyl 1-[1-(trifluoromethyl)cyclobutanecarbonyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)C1(C(F)(F)F)CCC1 SABBFVWMIYCPKH-UHFFFAOYSA-N 0.000 description 2
OTUUTWFORVRDSO-UHFFFAOYSA-N ethyl 4-[2-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-2-fluorobenzoate Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(CC)(F)CC)C1=CC(=C(C=C1)C(=O)OCC)F OTUUTWFORVRDSO-UHFFFAOYSA-N 0.000 description 2
LZVXFJHSFFUWGF-UHFFFAOYSA-N ethyl 4-[3-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-2-fluorobenzoate Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(CC)(F)CC)C1=CC(=C(C=C1)C(=O)OCC)F LZVXFJHSFFUWGF-UHFFFAOYSA-N 0.000 description 2
GPIKMXNVFPAFIE-UHFFFAOYSA-N ethyl 4-[6-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoate Chemical compound FC(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)OCC)C=C1)F)(CC)F GPIKMXNVFPAFIE-UHFFFAOYSA-N 0.000 description 2
OMGMQHZEFUYIMV-UHFFFAOYSA-N ethyl 4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoate Chemical compound C1=C(F)C(C(=O)OCC)=CC=C1C(C=N1)=CC=C1OCC1CCN(CC(F)(CC)CC)CC1 OMGMQHZEFUYIMV-UHFFFAOYSA-N 0.000 description 2
RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 2
KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
150000002222 fluorine compounds Chemical group 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000003914 insulin secretion Effects 0.000 description 2
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
229960003105 metformin Drugs 0.000 description 2
238000000034 method Methods 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
BXQKHNPVDWEROF-HKBQPEDESA-N methyl (2S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxylate Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@](CCC1)(C(=O)OC)C BXQKHNPVDWEROF-HKBQPEDESA-N 0.000 description 2
KLIYVIWMYYVFON-YWEHKCAJSA-N methyl (2S,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC)(CC)F KLIYVIWMYYVFON-YWEHKCAJSA-N 0.000 description 2
IVRQYBKUNSRKAS-BWKNWUBXSA-N methyl (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound C(C)C(CN1CCC(CC1)COC=1C=NC(=NC=1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)OC)C=C1)F)(CC)F IVRQYBKUNSRKAS-BWKNWUBXSA-N 0.000 description 2
IIHTYBPYSKMJSI-QPPBQGQZSA-N methyl (2S,4R)-1-[4-[6-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound FC(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)OC)C=C1)F)(CC)F IIHTYBPYSKMJSI-QPPBQGQZSA-N 0.000 description 2
CVSVNNMQRCHDCY-HOFKKMOUSA-N methyl (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxylate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=C(C=CC=1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)OC)(CC)F CVSVNNMQRCHDCY-HOFKKMOUSA-N 0.000 description 2
BZSITJNWQMLPLM-UHFFFAOYSA-N methyl 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-2-fluorophenyl]benzoate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC(=C(C=C1)C1=CC=C(C=C1)C(=O)OC)F)(CC)F BZSITJNWQMLPLM-UHFFFAOYSA-N 0.000 description 2
PDRBBZDXWAATPO-UHFFFAOYSA-N methyl 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-3-fluorophenyl]-2-fluorobenzoate Chemical compound C(C)C(CN1CCC(CC1)COC1=C(C=C(C=C1)C1=CC(=C(C=C1)C(=O)OC)F)F)(CC)F PDRBBZDXWAATPO-UHFFFAOYSA-N 0.000 description 2
ITAWMLAWTYGWRD-UHFFFAOYSA-N methyl 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-3-fluorobenzoate Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(C=2C(=CC(=CC=2)C(=O)OC)F)C=C1 ITAWMLAWTYGWRD-UHFFFAOYSA-N 0.000 description 2
FLOLBJULCHLQTO-UHFFFAOYSA-N methyl 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoate Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC(=C(C(=O)OC)C=C1)F)(CC)F FLOLBJULCHLQTO-UHFFFAOYSA-N 0.000 description 2
FIPIGPYNVLIBHM-UHFFFAOYSA-N methyl 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-3-fluorobenzoate Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=C(C=C(C(=O)OC)C=C1)F)(CC)F FIPIGPYNVLIBHM-UHFFFAOYSA-N 0.000 description 2
DHYPHCRIGNCWCN-UHFFFAOYSA-N methyl 4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-3-fluorobenzoate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=C(C=C(C(=O)OC)C=C1)F)(CC)F DHYPHCRIGNCWCN-UHFFFAOYSA-N 0.000 description 2
BOWVQLFMWHZBEF-KTKRTIGZSA-N oleoyl ethanolamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCCO BOWVQLFMWHZBEF-KTKRTIGZSA-N 0.000 description 2
XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 2
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238000011160 research Methods 0.000 description 2
230000028327 secretion Effects 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
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SFBUVAZNGQFFEC-MHZLTWQESA-N (2S)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxylic acid Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)O)C)C=CC(=C1)C1=NC=C(C=N1)OCC1CCN(CC1)CC(C)(C)F SFBUVAZNGQFFEC-MHZLTWQESA-N 0.000 description 1
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DSDQKWZDXVJAQM-LVXARBLLSA-N methyl (2S,4S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxylate Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)OC DSDQKWZDXVJAQM-LVXARBLLSA-N 0.000 description 1
RYBVAFCFYDBBAS-YXWJGHJBSA-N methyl (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-fluoropyrrolidine-2-carboxylate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC=1)(C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)OC)F)(CC)F RYBVAFCFYDBBAS-YXWJGHJBSA-N 0.000 description 1
ADJGFSMEAPXQLW-IYSWYEEDSA-N methyl (2r,4r)-4-hydroxy-2-methylpyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@]1(C)C[C@@H](O)CN1 ADJGFSMEAPXQLW-IYSWYEEDSA-N 0.000 description 1
YCYWAVUCBMJUPK-FJXQXJEOSA-N methyl (2s)-2-methylpyrrolidine-2-carboxylate;hydrochloride Chemical compound [Cl-].COC(=O)[C@]1(C)CCC[NH2+]1 YCYWAVUCBMJUPK-FJXQXJEOSA-N 0.000 description 1
ADJGFSMEAPXQLW-VDTYLAMSSA-N methyl (2s,4r)-4-hydroxy-2-methylpyrrolidine-2-carboxylate Chemical compound COC(=O)[C@]1(C)C[C@@H](O)CN1 ADJGFSMEAPXQLW-VDTYLAMSSA-N 0.000 description 1
SNNUJJOVUWILIG-UHFFFAOYSA-N methyl 1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-4-hydroxypiperidine-2-carboxylate Chemical compound FC1=C(C(=O)N2C(CC(CC2)O)C(=O)OC)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F SNNUJJOVUWILIG-UHFFFAOYSA-N 0.000 description 1
ZORHSASAYVIBLY-UHFFFAOYSA-N methyl 4-hydroxypyrrolidine-2-carboxylate Chemical compound COC(=O)C1CC(O)CN1 ZORHSASAYVIBLY-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
SRJOCJYGOFTFLH-UHFFFAOYSA-M piperidine-4-carboxylate Chemical compound [O-]C(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-M 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
108091006084 receptor activators Proteins 0.000 description 1
230000009467 reduction Effects 0.000 description 1
150000003335 secondary amines Chemical group 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000001467 thiazolidinediones Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Diabetes (AREA)
Epidemiology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Obesity (AREA)
Hematology (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

ES14866648T 2013-11-26 2014-11-25 Derivados de amida para el agonista del GPR119 Active ES2731823T3 (es)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
KR20130144601		2013-11-26
PCT/KR2014/011356 WO2015080446A1 (en)	2013-11-26	2014-11-25	Amide derivatives for gpr119 agonist

Publications (1)

Publication Number	Publication Date
ES2731823T3 true ES2731823T3 (es)	2019-11-19

Family

ID=53199342

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES14866648T Active ES2731823T3 (es)	2013-11-26	2014-11-25	Derivados de amida para el agonista del GPR119

Country Status (20)

Country	Link
US (1)	US9776987B2 (da)
EP (1)	EP3074384B1 (da)
JP (1)	JP6182269B2 (da)
KR (1)	KR101700906B1 (da)
CN (2)	CN105873916B (da)
AU (1)	AU2014354488B2 (da)
BR (1)	BR112016011999A2 (da)
CA (1)	CA2930850C (da)
DK (1)	DK3074384T3 (da)
ES (1)	ES2731823T3 (da)
HR (1)	HRP20191246T1 (da)
HU (1)	HUE045926T2 (da)
MX (1)	MX366297B (da)
NZ (1)	NZ720304A (da)
PH (1)	PH12016500980A1 (da)
PL (1)	PL3074384T3 (da)
PT (1)	PT3074384T (da)
RU (1)	RU2642429C2 (da)
TR (1)	TR201908098T4 (da)
WO (1)	WO2015080446A1 (da)

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* Cited by examiner, † Cited by third party
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IL295825A (en)	2020-02-28	2022-10-01	Kallyope Inc	gpr40 agonists
WO2021236617A1 (en)	2020-05-19	2021-11-25	Kallyope, Inc.	Ampk activators
CA3183575A1 (en)	2020-06-26	2021-12-30	Iyassu Sebhat	Ampk activators

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EP1326854B1 (en)	2000-10-20	2004-06-23	MERCK PATENT GmbH	Chiral binaphthol derivatives
DE102004037515A1 (de)	2003-08-22	2005-03-17	Merck Patent Gmbh	Verfahren zur Herstellung von Aldehyden
US20080103123A1 (en)	2006-08-30	2008-05-01	Biovitrum	New compounds
ATE528300T1 (de) *	2006-12-06	2011-10-15	Glaxosmithkline Llc	Bizyklische verbindungen und ihre verwendung als antidiabetika
US20100048632A1 (en)	2007-01-04	2010-02-25	Matthew Colin Thor Fyfe	Piperidine GPCR Agonists
AU2008279447A1 (en)	2007-07-19	2009-01-29	Metabolex, Inc.	N-azacyclic substituted pyrrole, pyrazole, imidazole, triazole and tetrazole derivatives as agonists of the RUP3 or GPR119 receptor for the treatment of diabetes and metabolic disorders
RU2443699C2 (ru)	2007-09-20	2012-02-27	Айрм Ллк	Соединения и композиции в качестве модуляторов активности gpr119
WO2009106565A1 (en)	2008-02-27	2009-09-03	Biovitrum Ab (Publ)	Agonists of gpr119
WO2009106561A1 (en)	2008-02-27	2009-09-03	Biovitrum Ab (Publ)	Pyrazine compounds for treating gpr119 related disorders
MX2011000392A (es)	2008-07-11	2011-03-01	Irm Llc	4-fenoxi-metil-piperidinas como moduladoras de la actividad de gpr119.
WO2010048149A2 (en)	2008-10-20	2010-04-29	Kalypsys, Inc.	Heterocyclic modulators of gpr119 for treatment of disease
AR077642A1 (es)	2009-07-09	2011-09-14	Arena Pharm Inc	Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo
AR077638A1 (es) *	2009-07-15	2011-09-14	Lilly Co Eli	Compuesto de (metanosulfonil -piperidin )-( alcoxi-aril) -tetrahidro- piridina , composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para el tratamiento de diabetes u obesidad
AU2011237775A1 (en)	2010-04-06	2012-11-22	Arena Pharmaceuticals, Inc.	Modulators of the GPR119 receptor and the treatment of disorders related thereto
WO2011145718A1 (ja)	2010-05-21	2011-11-24	田辺三菱製薬株式会社	新規ピロロ［２，３－ｄ］ピリミジン化合物
TW201202230A (en)	2010-05-24	2012-01-16	Mitsubishi Tanabe Pharma Corp	Novel quinazoline compound
CN102432598A (zh)	2010-09-29	2012-05-02	江苏恒瑞医药股份有限公司	三环化合物、其制备方法及其在医药上的应用
US9000175B2 (en)	2010-11-26	2015-04-07	Lupin Limited	Bicyclic GPR119 modulators
WO2012077655A1 (ja) *	2010-12-07	2012-06-14	塩野義製薬株式会社	Ｇｐｒ１１９アゴニスト活性を有するスピロ誘導体
JP2014159376A (ja)	2011-06-17	2014-09-04	Taisho Pharmaceutical Co Ltd	アザスピロアルカン化合物
PT2858986T (pt) *	2012-06-12	2019-11-29	Chong Kun Dang Pharmaceutical Corp	Derivados de piperidina como agonistas de gpr119
JP5892245B2 (ja) *	2012-06-13	2016-03-23	日産自動車株式会社	車両の駆動力制御装置及び駆動力制御方法

2014
- 2014-11-25 MX MX2016006904A patent/MX366297B/es active IP Right Grant
- 2014-11-25 PT PT14866648T patent/PT3074384T/pt unknown
- 2014-11-25 RU RU2016125492A patent/RU2642429C2/ru active
- 2014-11-25 NZ NZ720304A patent/NZ720304A/en not_active IP Right Cessation
- 2014-11-25 HR HRP20191246TT patent/HRP20191246T1/hr unknown
- 2014-11-25 JP JP2016534127A patent/JP6182269B2/ja not_active Expired - Fee Related
- 2014-11-25 CN CN201480064763.0A patent/CN105873916B/zh not_active Expired - Fee Related
- 2014-11-25 US US15/039,226 patent/US9776987B2/en not_active Expired - Fee Related
- 2014-11-25 EP EP14866648.0A patent/EP3074384B1/en active Active
- 2014-11-25 DK DK14866648.0T patent/DK3074384T3/da active
- 2014-11-25 KR KR1020140164986A patent/KR101700906B1/ko not_active Expired - Fee Related
- 2014-11-25 BR BR112016011999A patent/BR112016011999A2/pt active Search and Examination
- 2014-11-25 ES ES14866648T patent/ES2731823T3/es active Active
- 2014-11-25 TR TR2019/08098T patent/TR201908098T4/tr unknown
- 2014-11-25 PL PL14866648T patent/PL3074384T3/pl unknown
- 2014-11-25 WO PCT/KR2014/011356 patent/WO2015080446A1/en not_active Ceased
- 2014-11-25 AU AU2014354488A patent/AU2014354488B2/en not_active Ceased
- 2014-11-25 CA CA2930850A patent/CA2930850C/en not_active Expired - Fee Related
- 2014-11-25 CN CN201910451096.6A patent/CN110028494A/zh active Pending
- 2014-11-25 HU HUE14866648A patent/HUE045926T2/hu unknown
2016
- 2016-05-26 PH PH12016500980A patent/PH12016500980A1/en unknown

Also Published As

Publication number	Publication date
HRP20191246T1 (hr)	2019-12-27
US20170129875A1 (en)	2017-05-11
NZ720304A (en)	2017-08-25
KR20150060573A (ko)	2015-06-03
CN105873916A (zh)	2016-08-17
CA2930850C (en)	2017-05-16
DK3074384T3 (da)	2019-07-15
PH12016500980B1 (en)	2016-06-20
JP2016538296A (ja)	2016-12-08
US9776987B2 (en)	2017-10-03
CA2930850A1 (en)	2015-06-04
WO2015080446A1 (en)	2015-06-04
EP3074384B1 (en)	2019-05-22
KR101700906B1 (ko)	2017-01-31
HUE045926T2 (hu)	2020-01-28
EP3074384A1 (en)	2016-10-05
RU2016125492A (ru)	2018-01-09
JP6182269B2 (ja)	2017-08-16
AU2014354488A1 (en)	2016-06-09
PL3074384T3 (pl)	2019-09-30
MX2016006904A (es)	2016-10-28
BR112016011999A2 (pt)	2017-08-08
PH12016500980A1 (en)	2016-06-20
TR201908098T4 (tr)	2019-06-21
EP3074384A4 (en)	2017-04-19
CN110028494A (zh)	2019-07-19
CN105873916B (zh)	2019-08-27
RU2642429C2 (ru)	2018-01-25
AU2014354488B2 (en)	2017-08-24
MX366297B (es)	2019-07-04
PT3074384T (pt)	2019-07-10

Publication	Publication Date	Title
EP2858986B1 (en)	2019-10-30	Piperidine derivatives as gpr119 agonists
CA3069544A1 (en)	2019-01-31	Compounds and methods for the targeted degradation of androgen receptor
JP7834830B2 (ja)	2026-03-24	アミノピリジン誘導体およびそれらの選択的ａｌｋ－２阻害剤としての使用
ES2731823T3 (es)	2019-11-19	Derivados de amida para el agonista del GPR119
KR20230017787A (ko)	2023-02-06	Gpr39 단백질의 길항제
AU2020414202B2 (en)	2024-01-04	Novel amino aryl derivative useful as diacylglycerol acyltransferase 2 inhibitor and use thereof
TWI434830B (zh)	2014-04-21	一級胺二醇二氮烯鎓雜環衍生物
EP3444237B1 (en)	2020-10-28	Iridinesulfonamide compound and use method thereof
AU2013275090B2 (en)	2016-05-12	Piperidine derivatives for GPR119 agonist
HK40007931A (en)	2020-06-05	Amide derivative, stereoisomer thereof or pharmaceutically acceptable salt thereof, and composition comprising the same
WO2025106910A1 (en)	2025-05-22	Degrader molecules targeting androgen receptor
JPWO2021222858A5 (da)	2024-04-01
HK1225034B (zh)	2020-05-29	用於gpr119激动剂的酰胺衍生物
TW202540107A (zh)	2025-10-16	Ｍ４陽性變構調節劑
HK1225034A1 (en)	2017-09-01	Amide derivatives for gpr119 agonist